PB1880: ACUTE MYELOID LEUKEMIA WITH MUTATED NPM1 – A DIFFERENT ENTITY IN THE ELDERLY?
Authors: Rita S Gomes, Adriana Roque, Pedro Amorim Machado, Margarida Coucelo, Teresa Simões, Ana Oliveira, Telma Nascimento, Sandra Marini, Marta Pereira, Emilia Cortesão
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Acute myeloid leukemia (AML) with mutated Nucleophosmin-1 (NPM1MT) occurs in approximately 30% of patients (pts) with AML and usually carries a better prognosis. However, the positive prognostic impact of NPM1MT does not seem to extend to elderly pts. Aims: To analyse the impact of age in the clinical characteristics, outcomes, and prognosis of pts with AML with NPM1MT. Methods: Retrospective, single-centre study of 41 AML-NPM1MT pts diagnosed between jan/2015 and jul/2022. Clinical, cytogenetic and molecular data at diagnosis were analysed. The best cut-off point for age impact on overall survival (OS) was stipulated using receiver operating characteristic (ROC) curve – cut-off 60 years old (yo) (sensitivity 82%, specificity 78%, Area under the curve (AUC) 0.83). Results: We included 41 pts, 41% male, with a median age 60 (22-79) yo (54% [n=22 ≥60yo]). There were no differences between pts<60yo (YOUNG) or ≥60yo (OLD) regarding hyperleukocytosis (≥100x10^6/L WBC) (21 vs 32%; p=0.438), lactate dehydrogenase >2 x upper normal limit (74 vs 59%; p=0.326) and median NPM1 variant allele frequency (VAF) (45 vs 41%; p=0.147). Regarding conventional cytogenetics (available for 16 YOUNG and 20 OLD), no significant differences were observed (normal karyotype - 69% vs 65%; complex karyotype - 6% vs 25%; p=0.213). Concerning molecular alterations, 37 and 41% was FLT3-ITD positive, respectively (p= 0.790). Among 17 cases with NGS (Next Generation Sequencing) panel, 60 and 71%, respectively, had ≥2 mutations (p=0.840); none the mutations showed preponderance for age class. Considering European LeukemiaNet 2017 and 2022 risk classifications, OLD had higher proportion of patients in adverse risk stratum in ELN2017 (30 vs 6%; p=0.201) and ELN2022 (29 vs 6%; p=0.197), despite absence of statistical difference. Twenty-six pts (63%) received intensive chemotherapy (IC), 5 of whom also received midostaurin; and 3 (7%) received hypomethylating agents (HMA). The remaining pts (29%; n=12) received only best supportive care or died before any therapeutic. The 3 pts who received HMA were OLD, and only 36% OLD pts received IC. Considering pts receiving IC with available response evaluation after induction (n=26) – in IC cohort a higher proportion of YOUNG attained complete morphologic remission (CR) (100 vs 75%; p=0.027), but in CR pts, age had no impact in the proportion of negative MFC-MRD (multi-color flow-cytometry – minimal residual disease) (72 vs 71%; p= 0.968). Five pts (17%) were submitted to allogeneic stem cell transplantation, all of them YOUNG. The median OS for the global cohort was 12.9 months. OLD presented a lower OS (2.6 months vs not reached; HR 5.45; p<0.001; OS-6 months 36.4 vs 89.5%). This negative impact remains after adjusting for induction regimen (HR 4.36; p=0.004), although it loses its significance when we consider only pts submitted to IC (23.4 months vs not reached; HR 2.84; p=0.101; OS-6 months 75 vs 94.4%). The median OS for pts submitted to HMA was 8 months (OS 6M 67%). The main cause of death was infection in both groups (80 vs 39% for YOUNG and OLD, respectively; p=0.249). Summary/Conclusion: In our cohort, OLD pts who received IC had no statistically significant inferior OS. However, OLD were more frequently not eligible for IC, as expected. Despite the small simple size, HMA alone did not seem to be a good alternative, as seen before the approval of venetoclax. New combinations, namely HMA plus venetoclax are needed for these pts, despite the traditional good prognosis associated to NPM1MT. Keywords: Acute myeloid leukemia, Elderly